Nitrous oxide (N2O) is widely used by the dental profession for the control of patient anxiety. For years the gas was thought to be innocuous but is now known to have the potential of producing some serious side effects, especially on the hemopoietic and central nervous systems. It likely produces these effects by inactivating vitamin B12. Vitamin B12 is a co- factor in the synthesis of methionine, an amino acid that has many important roles, including that of being a precursor in the synthesis of the methyl donor, s-adenosylmethionine (SAMe). Thus, it is to be expected that sufficient exposure to N2O will lower tissue SAMe concentrations and do this in relation to the rate at which the methyl donor is consumed in transmethylation reactions. Furthermore, drugs that increase transmethylation would be expected to augment the decrease. Some preliminary studies in mice support this hypothesis, in that brain corpus striatum, which has a high rate of dopamine o-methylation, showed a decrease in SAMe concentrations distinct from that of cerebellum or cortex after exposure to N20 and when haloperidol, a drug known to increase striatal dopamine metabolism, was given to N2O-exposed mice, there was a decline in striatal SAMe that was greater than that produced by either agent alone. This study will enlarge upon these findings and include several different experimental approaches to study the influence of other drugs known to increase transmethylation on tissue SAMe in N2O-exposed mice. Findings from these studies might provide information which could be important to understanding how to more safely use N2O.